FDA Approves Acalabrutinib for Mantle Cell Lymphoma

The US Food and Drug Administration (FDA) has granted accelerated approval to the oral drug acalabrutinib (Calquence) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one previous therapy. The agent is approved at a recommended dose of 100 mg twice daily.

MCL is a rare type of lymphoma, representing 3% to 10% percent of all non-Hodgkin lymphoma cases in the United States, according to the National Cancer Institute. The approval comes less than 1 month after it was revealed that preclinical data on acalabrutinib were falsified.

The approval of acalabrutinib was based on the phase II ACE-LY-004 MCL trial, a single-arm, open-label study that included MCL patients (N = 124) who had been treated with at least one prior therapy. Acalabrutinib was administered orally twice daily at 100 mg, until either disease progression or unacceptable toxicity.

The investigator assessed overall response rate—the primary endpoint of the trial—was 80% (95% CI, 72%–87%), and 40% of patients achieved complete response (95% CI, 31%–49%). With over 15 months of follow-up, the median duration of response has not been reached. Median time to best response was 1.9 months.

“The acalabrutinib approval represents an important development for patients currently battling MCL, an aggressive type of blood cancer that is typically diagnosed at an advanced stage and associated with a high relapse rate,” said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston and principal investigator of the ACE-LY-004 MCL trial, in a press release. “In addition to the overall response rate, the high complete response rate of 40% seen in this trial illustrates the potential of acalabrutinib to help patients achieve a deep response.”

The most common (> 20%) adverse events (AEs) associated with acalabrutinib in the ACE-LY-004 MCL trial included anemia, bruising, diarrhea, fatigue, headache, myalgia, neutropenia, and thrombocytopenia. Dose reductions or discontinuations due to AEs were reported in 1.6% and 6.5% of patients, respectively. The most frequently reported (≥ 5%) grade 3/4 AEs were anemia, neutropenia, and thrombocytopenia.